Effect of Phosphatidylcholine and Cholesterol on pH-Sensitive Liposomes.

Hazemoto, Norio; Harada, Masanobu; Suzuki, Shigeki; Kaiho, Fusao; Haga, Makoto; Kato, Yuriko

doi:10.1248/cpb.41.1003

Cited by 15 publications

(8 citation statements)

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“…For decades, this mechanism has been exploited to develop pH-sensitive liposomes that are made up of phosphatidylethanolamine (PE) and phosphatidylcholine (PC) and their derivatives. [31][32][33][34][35] It is believed that at a lower pH these phospholipids are unable to form bilayered vesicles, thereby resulting in the release of their aqueous contents. Included in this series are both anionic and cationic liposomes.…”

Section: Ph Sensitive Liposomesmentioning

confidence: 99%

Liposomes: Versatile and Biocompatible Nanovesicles for Efficient Biomolecules Delivery

Mallick¹,

Choi²

2014

j. nanosci. nanotech.

139

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Since the revolutionary discovery that phospholipids can form closed bilayered structures in aqueous systems, liposomes have become a very interesting topic of research. Because of their versatility and amazing biocompatibility, the use of liposomes has been widely accepted in many scientific disciplines. Their applications, especially in medicine, have yielded breakthroughs with anticancer-drug carriers over the past few decades. Specifically, their easy preparation and various structural aspects have given rise to a broadly usable way to internalize biomolecules such as drugs, DNA, RNA and even imaging probes. This review article reports recent developments in liposomal drug delivery and gene delivery, and thoroughly covers the synthesis and different kinds of liposomal surface modification techniques that have resulted in higher stability and efficiency with respect to the use of liposomes in tumor cell targeting, site-specific release, and extending blood retention times.

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Section: Ph Sensitive Liposomesmentioning

confidence: 99%

Liposomes: Versatile and Biocompatible Nanovesicles for Efficient Biomolecules Delivery

Mallick¹,

Choi²

2014

j. nanosci. nanotech.

139

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“…pH sensitivity was observed only when the molar ratio of PtdCho in liposomes was less than 0.32; moreover, curves of leakage against pH were shifted to the more acidic regions as the PtdCho content of the liposomes increased. In other words, under acidic conditions a high PtdCho content of the membrane was needed to prevent leakage of the contents [37]. Thus changes in the phospholipid composition of the plasma membrane may be part of the yeast's response to adapt to acidic environmental conditions.…”

Section: Effects Of Phmentioning

confidence: 99%

Regulation of activity in vitro and in vivo of three phospholipases B from Saccharomyces cerevisiae

Merkel

Oskolkova

Raab

et al. 2005

Biochemical Journal

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The genome of the yeast, Saccharomyces cerevisiae, contains three highly similar genes coding for phospholipases B/lysophospholipases. These enzymes behave differently with respect to substrate preferences in vitro and relative contributions to phospholipid catabolism in vivo [Merkel, Fido, Mayr, Pruger, Raab, Zandonella, Kohlwein and Paltauf (1999) J. Biol. Chem. 274, 28121-28127]. It is shown in the present study that, in vitro, pH markedly affects the substrate preference of Plb1p and Plb2p, but not of Plb3p. At the pH optimum of 2.5-3.5, the order of substrate preference of Plb1p and Plb2p is PtdSer (phosphatidylserine)>PtdIns>PtdCho (phosphatidylcholine>PtdEtn (phosphatidylethanolamine). At pH values of 5 and above, the substrate preferences change to PtdCho=PtdEtn for Plb1p and PtdSer=PtdEtn for Plb2p. Accordingly, with cultured cells the ratio of PtdIns/PtdCho breakdown, as reflected in the ratio of GroPIns (glycerophosphoinositol)/GroPCho (glycerophosphocholine) released into the culture medium, is inversely related to the pH of the growth medium. This effect is ascribed to the pH response of Plb1p, because Plb2p does not contribute to the degradation of PtdIns and PtdCho in vivo. Bivalent and tervalent cations activate phospholipases B at pH 5.5, but are inhibitory at pH 2.5. Al3+ at a concentration of 20 mM increases Plb1p activity in vitro by 8-fold and leads to a 9-fold increase in GroPCho release by whole cells. In vivo, cycloheximide strongly inhibits the breakdown of PtdIns, and to a lesser extent PtdCho. However, Al3+-stimulated GroPCho release is almost completely inhibited by cycloheximide. Deletion of PLB3 leads to increased sensitivity to toxic Al3+. Addition of SDS or melittin to cultured cells leads to a significant increase in phospholipid degradation, which is insensitive to inhibition by cycloheximide. Deletion mutants defective in the PLB1 gene are significantly more resistant to SDS than are wild-type cells.

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“…Such impact of DSPE-PEG might have resulted from the fact that pKa values of the lipids with pH-sensitive head groups decreased with the change of electrical ® eld by DSPE-PEG. The pH sensitivity of liposomes has been reported to be due to protonation of pH-sensitive lipid head groups (Hazemoto et al 1993). The higher impact of DSPE-PEG on the pH-sensitivity of DOPE}oleic acid liposomes could be explained by the possibility that DSPE-PEG might hinder the protonation of the head group of oleic acid to a greater extent.…”

Section: Effect Of Dspe-peg On the Ph Sensitivity Of Liposomesmentioning

confidence: 99%

pH-sensitive, serum-stable and long-circulating liposomes as a new drug delivery system

Hong

Lim

et al. 2002

Journal of Pharmacy and Pharmacology

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The lack of stability in blood and the short blood circulation time of pH-sensitive liposomes are major drawbacks for their application in-vivo. To develop pH-sensitive, serum-stable and longcirculating liposomes as drug delivery systems, the impact of polyethylene glycol-derived phosphatidylethanolamine (DSPE-PEG) on the properties of pH-sensitive liposomes was investigated. pH-sensitive liposomes were prepared with dioleoylphosphatidylethanolamine (DOPE) and oleic acid (DOPE/oleic acid liposome) or DOPE and 1,2-dipalmitoylsuccinylglycerol (DOPE/DPSG liposome). The inclusion of DSPE-PEG enhanced the serum stability of both DOPE/oleic acid and DOPE/DPSG liposomes, but also shifted the pH-response curve of pHsensitive liposomes to more acidic regions and reduced the maximum leakage percentage. The impact of DSPE-PEG, however, was much lower in the DOPE/DPSG liposomes than in the DOPE/oleic acid liposomes. In tumour tissue homogenates, where the pH is lower than normal healthy tissues, the pH-sensitive DOPE/DPSG liposomes released the entrapped markers rapidly, in comparison with pH-insensitive dipalmitoylphosphatidylcholine/cholesterol/DSPE-PEG liposomes. Moreover, the release rate was not affected by the content of DSPE-PEG. The blood circulation time of methotrexate incorporated in DOPE/DPSG liposomes was signi cantly prolonged with increasing content of DSPE-PEG. Taken together, the liposomes composed of DOPE, DPSG and DSPE-PEG (up to 5 %) were pH sensitive, plasma stable and had a long circulation time in the blood. The complete destabilization of the liposomes at tumour tissues suggests that the liposomes might be useful for the targeted delivery of drugs such as anticancer agents.

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Effect of Phosphatidylcholine and Cholesterol on pH-Sensitive Liposomes.

Cited by 15 publications

References 0 publications

Liposomes: Versatile and Biocompatible Nanovesicles for Efficient Biomolecules Delivery

Liposomes: Versatile and Biocompatible Nanovesicles for Efficient Biomolecules Delivery

Regulation of activity in vitro and in vivo of three phospholipases B from Saccharomyces cerevisiae

pH-sensitive, serum-stable and long-circulating liposomes as a new drug delivery system

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